Phase 1 64Cu-DOTA-pembrolizumab PET radiotracer targets PD-1 to guide SBRT decisions

City of Hope is running this Phase 1 pilot to test safety, feasibility, and imaging performance of 64Cu‑DOTA‑pembrolizumab (64CDP)—a PET radiotracer made by chelating copper‑64 to pembrolizumab (Merck/MSD’s PD‑1–blocking monoclonal antibody) so PD‑1–binding signal can be visualized on PET. Patients with stage IV NSCLC who are already on standard pembrolizumab and have oligo-progressive disease planned for SBRT undergo 64CDP dosing and serial PET imaging around the SBRT window, with the aim of distinguishing true progression from treatment-related changes and measuring how uptake changes pre/post-radiation. The intervention sequence layers investigational imaging onto standard systemic therapy (pembrolizumab) plus local therapy (SBRT), with optional low-dose radiation therapy (LDRT) based on the first 64CDP scan. The main scientific angle is using an immunotherapy antibody as an on-treatment, lesion-level PET biomarker to potentially personalize which progressing sites get intensified local therapy while continuing effective systemic PD-1 blockade. In practice today, oligoprogression on pembrolizumab is commonly managed by continuing immunotherapy and ablating a few progressing lesions with SBRT (or switching systemic therapy if progression is more diffuse), and this study explores whether PD‑1–targeted PET can sharpen those calls.